Before the 1950's, most pharmaceutical tablets were manufactured by granulating the active ingredients and diluents together with suitable binders. The purpose of doing so was to produce free flowing compressible granules well suited for tabletting in a tabletting press. For many new formulations, this cumbersome and long traditional process of granulation is now being replaced by direct compression.
Early in the development of direct compression preparation of pharmaceutical dosage forms, only a few chemicals (NaCl, NaBr, KBr and methanamine) possessed the necessary flow, cohesion and lubricating properties to form tablets. Direct compression later evolved, however, to become a process by which tablets are compressed directly from a mixture of a wide variety of specially processed fillers, lubricants and disintegrants which can flow uniformly into a die cavity.
Some of the known direct compression diluents include sugars such as fructose, maltose, dextrose and other polysaccharides, calcium gluconate, calcium carbonate, powdered oyster shells, calcium phosphate, and polymers such as microcrystalline cellulose and other cellulose derivatives. Although most of these diluents are chemically inert, many of them have certain drawbacks. The sugar-based diluents are hygroscopic and their compression property is significantly dependent on the amount of moisture present in the diluents. The calcium salts are alkaline and may cause unwanted chemical reactions with certain types of acidic drugs.
Other direct compression diluents, including waxes, are also known. Several wax formulations have been widely accepted for use in drug dosage forms. These waxes include, for example, carnauba wax, beeswax, glyceride esters, hydrogenated vegetable as well as animal oils, stearyl alcohols and their derivatives, polyethylene glycols and their derivatives, esters of fatty acids such as palmitic acid, stearic acid, oleic acid, linoleic acid, linolenic acid, etc. These waxes are usually if not always chemically inert, can impart sustained release characteristics when required and, as drug diluents, provide a level of cohesion which approaches the ideal when active agents are combined with them and compressed into dosage forms.
The disadvantage with waxes inheres in their flow properties, however. Although melted waxes have satisfactory flow properties under some circumstances, most waxes tend to clump, not flow, and as such are generally inappropriate for use in tabletting presses and similar production machinery even when attempts are made to grate or divide them. In fact, they are difficult to transfer, ship, store and dispense for this reason, also. In addition, of course, certain drugs should not be exposed even to the relatively low "melt heat" of a wax, for drug stability or other reasons. A free-flowing granulated wax is therefore the theoretical ideal as a diluent for incorporation into a compressed drug-containing matrix.
U.S. Pat. No. 4,590,062 to Jang, entitled "Dry Direct Compression Compositions for Controlled Release Dosage Forms," discloses combinations of waxes and certain additional diluents which can be direct compressed with an active agent to prepare a controlled release tablet. The waxes and additional diluents may be slugged together and granulated, and flow aid materials such as finely divided silica or talc, in amounts between 0.5 and 2% by weight, may be included to improve the flow properties of the resulting wax granules. The diluent wax-containing granules are disclosed by Jang as suitable for combination with a wide range of biological and pharmaceutical active agents.